Lighting up Tumors with Receptor-Specific Optical Molecular Probes

Abstract

Accurate and rapid detection of tumors is of great importance for interrogating the molecular basis of cancer pathogenesis, preventing the onset of complications, and implementing a tailored therapeutic regimen. In this era of molecular medicine, molecular probes that respond to, or target molecular processes are indispensable. Although numerous imaging modalities have been developed for visualizing pathologic conditions, the high sensitivity and relatively innocuous low energy radiation of optical imaging method makes it attractive for molecular imaging. While many human diseases have been studied successfully by using intrinsic optical properties of normal and pathologic tissues, molecular imaging of the expression of aberrant genes, proteins, and other pathophysiologic processes would be enhanced by the use of highly specific exogenous molecular beacons. This review focuses on the development of receptor-specific molecular probes for optical imaging of tumors. Particularly, bioconjugates of probes that absorb and fluoresce in the near infrared wavelengths between 750 and 900 nm will be reviewed.

Keywords

Optical imaging Contrast agents Molecular probes Carbocyanine dyes Cell surface receptors Somatostatin Bombesin Folate Epidermal growth factor Neurotensin

References

Shah

Cerussi

Eker

Espinoza

Butler

Noninvasive Functional Optical Spectroscopy of Human Breast Tissue. Proc. Natl. Acad. Sci. USA 98, 4420–4425 (2001).

Hawrysz

D. J.

and Sevick-Muraca

E. M.

Developments Toward Diagnostic Breast Cancer Imaging Using Near-infrared Optical Measurements and Fluorescent Contrast Agents. Neoplasia 2, 388–417 (2000).

Ntziachristos

Tung

C. H.

Bremer

and Weissleder

Fluorescence Molecular Tomography Resolves Protease Activity In Vivo. Nat Med 8, 757–760 (2002).

Hebden

J. C.

Veenstra

Dehghani

Hillman

E. M. C.

Schweiger

Three-dimensional Time-resolved Optical Tomography of a Conical Breast Phantom. Appl. Optics 40, 3278–3287 (2001).

Culver

J. P.

Ntziachristos

Holboke

M. J.

and Yodh

A. G.

Optimization of Optode Arrangements for Diffuse Optical Tomography: A Singular-value Analysis. Opt. Lett. 26, 701–703 (2001).

Hyde

D. E.

Farrell

T. J.

Patterson

M. S.

and Wilson

B. C.

A Diffusion Theory Model of Spatially Resolved Fluorescence From Depth-dependent Fluorophore Concentrations. Phys. Med. Biol. 46, 369–383 (2001).

Pogue

B. W.

Geimer

McBride

T. O.

Jiang

S. D.

Osterberg

U. L.

Three-dimensional Simulation of Near-infrared Diffusion in Tissue: Boundary Condition and Geometry Analysis for Finite-element Image Reconstruction. Appl. Optics 40, 588–600 (2001).

McBride

T. O.

Pogue

B. W.

Gerety

E. D.

Poplack

S. B.

Osterberg

U. L.

Spectroscopic Diffuse Optical Tomography for the Quantitative Assessment of Hemoglobin Concentration and Oxygen Saturation in Breast Tissue. Appl. Optics 38, 5480–5490 (1999).

Schotland

J. C.

Continuous-wave Diffusion Imaging. J. Opt. Soc. Am. A-Opt. Image Sci. Vis. 14, 275–279 (1997).

10.

Lee

and Sevick-Muraca

Fluorescence-enhanced Absorption Imaging Using Frequency-domain Photon Migration: Tolerance to Measurement Error. J. Biomed. Opt. 6, 58–67 (2001).

11.

Cheong

W. F.

vanHouten

J. P.

Kermit

E. L.

Machold

T. R.

Stevenson

D. K.

Pilot Comparison of Light-based Optical Tomography Versus Ultrasound for Real-time Imaging of Neonatal Intraventricular Hemorrhage. Pediatr. Res. 39, 1189–1189 (1996).

12.

Rhine

W. D.

Benaron

D. A.

Darceuil

H. E.

deCrespigny

Cheong

W. F.

Simultaneous Time of-flight Adjusted (TOFA) Near-infrared Spectroscopy and Magnetic Resonance Imaging of Immature Rabbit Hypoxic-ischemic Encephalopathy (HIE). Pediatr. Res. 39, 2264–2264 (1996).

13.

Wagnieres

G. A.

Star

W. M.

and Wilson

B. C.

In Vivo Fluorescence Spectroscopy and Imaging for Oncological Applications. Photochem. Photobiol. 68, 603–632 (1998).

14.

Ntziachristos

Yodh

A. G.

Schnall

and Chance

Concurrent MRI and Diffuse Optical Tomography of Breast After Indocyanine Green Enhancement. Proc. Natl. Acad. Sci. USA 97, 2767–2772 (2000).

15.

Cubeddu

Pifferi

Taroni

Torricelli

Valentini

Fluorescence Imaging During Photodynamic Therapy of Experimental Tumors in Mice Sensitized with Disulfonated Aluminum Phthalocyanine. Photochem. Photobiol. 72, 690–695 (2000).

16.

Cerussi

A. E.

Jakubowski

Shah

Bevilacqua

Lanning

Spectroscopy Enhances the Information Content of Optical Mammography. J. Biomed. Opt. 7, 60–71 (2002).

17.

Villringer

and Chance

Non-invasive Optical Spectroscopy and Imaging of Human Brain Function. Trends Neurosci. 20, 435–442 (1997).

18.

Tromberg

B. J.

Shah

Lanning

Cerussi

Espinoza

Non-invasive In Vivo Characterization of Breast Tumors Using Photon Migration Spectroscopy. Neoplasia 2, 26–40 (2000).

19.

Young

A. R.

Chromophores in Human Skin. Phys. Med. Biol. 42, 789–802 (1997).

20.

Brancaleon

Durkin

A. J.

J. H.

Menaker

Fallon

J. D.

In Vivo Fluorescence Spectroscopy of Nonmelanoma Skin Cancer. Photochem. Photobiol. 73, 178–183 (2001).

21.

Contag

C. H.

and Bachmann

M. H.

Advances In Vivo Bioluminescence Imaging of Gene Expression. Annu. Rev. Biomed. Eng. 4, 235–260 (2002).

22.

Soling

and Rainov

N. G.

Bioluminescence Imaging In Vivo — Application to Cancer Research. Expert Opinion on Biological Therapy 3, 1163–1172 (2003).

23.

Zimmer

Green Fluorescent Protein (GFP): Applications, Structure, and Related Photophysical Behavior. Chem. Rev. 102, 759–781 (2002).

24.

Y. A.

Timiryasova

Zhang

Beltz

and Szalay

A. A.

Optical Imaging: Bacteria, Viruses, and Mammalian Cells Encoding Light-emitting Proteins Reveal the Locations of Primary Tumors and Metastases in Animals. Anal. Bioanal. Chem. 377, 964–972 (2003).

25.

Hoffman

R. M.

Green Fluorescent Protein Imaging of Tumour Growth, Metastasis, and Angiogenesis in Mouse Models. Lancet Oncology 3, 546–556 (2002).

26.

Hoffman

R. M.

Green Fluorescent Protein Imaging of Tumor Cells in Mice. Lab Anim. 31, 34–41 (2002).

27.

Bremer

Ntziachristos

and Weissleder

Optical-based Molecular Imaging: Contrast Agents and Potential Medical Applications. Eur. Radiol. 13, 231–243 (2003).

28.

Bogdanov

A. A.

Lin

C. P.

Simonova

Matuszewski

and Weissleder

Cellular Activation of the Self-quenched Fluorescent Reporter Probe in Tumor Microenvironment. Neoplasia 4, 228–236 (2002).

29.

Funovics

Weissleder

and Tung

C. H.

Protease Sensors for Bioimaging. Anal. Bioanal. Chem. 377, 956–963 (2003).

30.

Mahmood

and Weissleder

Near-infrared Optical Imaging of Proteases in Cancer. Mol. Cancer Ther. 2, 489–496 (2003).

31.

Weissleder

Scaling Down Imaging: Molecular Mapping of Cancer in Mice. Nat. Rev. Cancer 2, 11–18 (2002).

32.

Brigger

Dubernet

and Couvreur

Nanoparticles in Cancer Therapy and Diagnosis. Adv. Drug Deliv. Rev. 54, 631–651 (2002).

33.

Sahoo

S. K.

and Labhasetwar

Nanotech Approaches to Delivery and Imaging Drug. Drug Discov. Today 8, 1112–1120 (2003).

34.

West

J. L.

and Halas

N. J.

Engineered Nanomaterials for Biophotonics Applications: Improving Sensing, Imaging, and Therapeutics. Annu. Rev. Biomed. Eng. 5, 285–292 (2003).

35.

Chan

W. C. W.

Maxwell

D. J.

Gao

X. H.

Bailey

R. E.

Han

M. Y.

Luminescent Quantum Dots for Multiplexed Biological Detection and Imaging. Curr. Opin. Biotechnol. 13, 40–46 (2002).

36.

Gao

X. H.

and Nie

S. M.

Molecular Profiling of Single Cells and Tissue Specimens with Quantum Dots. Trends Biotechnol. 21, 371–373 (2003).

37.

Benaron

D. A.

The Future of Cancer Imaging. Cancer Metastasis Rev. 21, 45–78 (2002).

38.

Frangioni

J. V.

In Vivo Near-infrared Fluorescence Imaging. Curr. Opin. Chem. Biol. 7, 626–634 (2003).

39.

Sevick-Muraca

E. M.

Houston

J. P.

and Gurfinkel

Fluorescence-enhanced, Near Infrared Diagnostic Imaging with Contrast Agents. Curr. Opin. Chem. Biol. 6, 642–650 (2002).

40.

Weissleder

and Mahmood

Molecular Imaging. Radiology 219, 316–333 (2001).

41.

Granberg

Sundin

Janson

E. T.

Oberg

Skogseid

Octreoscan in Patients with Bronchial Carcinoid Tumours. Clin. Endocrinol. 59, 793–799 (2003).

42.

Arsene

Giraudeau

Le Lez

M. L.

Pisella

P. J.

Pourcelot

Follow Up by Colour Doppler Imaging of 102 Patients with Retinal Vein Occlusion Over 1 Year. Br. J. Ophthalmol. 86, 1243–1247 (2002).

43.

Kaiser

R. S.

Berger

J. W.

Williams

G. A.

Tolentino

M. J.

Maguire

A. M.

Variability in Fluorescein Angiography Interpretation for Photodynamic Therapy in Age-related Macular Degeneration. Retin.-J. Retin. Vitr. Dis. 22, 683–690 (2002).

44.

Pflugfelder

S. C.

Solomon

and Stern

M. E.

The Diagnosis and Management of Dry eye — A Twenty-five Year Review. Cornea 19, 644–649 (2000).

45.

Raabe

Beck

Gerlach

Zimmermann

and Seifert

Near-infrared Indocyanine Green Video Angiography: A New Method for Intraoperative Assessment of Vascular Flow. Neurosurgery 52, 132–139 (2003).

46.

Shaikh

Ruby

A. J.

and Williams

G. A.

Photodynamic Therapy using Verteporfin for Choroidal Neovascularization in Angioid Streaks. Am. J. Ophthalmol. 135, 1–6 (2003).

47.

Tsilou

Csaky

Rubin

B. I.

Gahl

and Kaiser-Kupfer

Retinal Visualization in an Eye with Corneal Crystals using Indocyanine Green Videoangiography. Am. J. Ophthalmol. 134, 123–125 (2002).

48.

Achilefu

Dorshow

R. B.

Bugaj

J. E.

and Rajagopalan

Novel Receptor-targeted Fluorescent Contrast Agents for In Vivo Tumor Imaging. Invest. Radiol. 35, 479–485 (2000).

49.

Gurfinkel

Thompson

A. B.

Ralston

Troy

T. L.

Moore

A. L.

Pharmacokinetics of ICG and HPPH-car for the Detection of Normal and Tumor Tissue using Fluorescence, Near-infrared Reflectance Imaging: A Case Study. Photochem. Photobiol. 72, 94–102 (2000).

50.

Intes

Ripoll

Chen

Nioka

Yodh

A. G.

In Vivo Continuous-wave Optical Breast Imaging Enhanced with Indocyanine Green. Med. Phys. 30, 1039–1047 (2003).

51.

Malicka

Gryczynski

Geddes

C. D.

and Lakowicz

J. R.

Metal-enhanced Emission from Indocyanine Green: A New Approach to In Vivo Imaging. J. Biomed. Opt. 8, 472–478 (2003).

52.

Cuccia

D. J.

Bevilacqua

Durkin

A. J.

Merritt

Tromberg

B. J.

In Vivo Quantification of Optical Contrast Agent Dynamics in Rat Tumors by Use of Diffuse Optical Spectroscopy with Magnetic Resonance Imaging Coregistration. Appl. Optics 42, 2940–2950 (2003).

53.

Mujumdar

R. B.

Ernst

L. A.

Mujumdar

S. R.

Lewis

C. J.

and Waggoner

A. S.

Cyanine Dye Labeling Reagents — Sulfoindocyanine Succinimidyl Esters. Bioconjugate Chem. 4, 105–111 (1993).

54.

Ballou

Fisher

G. W.

Waggoner

A. S.

Farkas

D. L.

Reiland

J. M.

Tumor Labeling In Vivo Using Cyanine-Conjugated Monoclonal-Antibodies. Cancer Immunol. Immunother. 41, 257–263 (1995).

55.

Hirata

Kogiso

Morimoto

Miyamoto

Taue

Synthesis and Reactivities of 3-indocyanine-green-acyl-1,3-thiazolidine-2-thione (ICG-ATT) as a New Near-infrared Fluorescent-labeling Reagent. Bioorg. Med. Chem. 6, 2179–2184 (1998).

56.

Lin

Y. H.

Weissleder

and Tung

C. H.

Novel Near-infrared Cyanine Fluorochromes: Synthesis, Properties, and Bioconjugation. Bioconjugate Chem. 13, 605–610 (2002).

57.

Pham

Lai

W. F.

Weissleder

and Tung

C. H.

High Efficiency Synthesis of a Bioconjugatable Near-infrared Fluorochrome. Bioconjugate Chem. 14, 1048–1051 (2003).

58.

Tarazi

George

Patonay

and Strekowski

Spectral Characterization of a Novel Near-infrared Cyanine Dye: A Study of its Complexation with Metal Ions. Talanta 46, 1413–1424 (1998).

59.

Gorecki

Patonay

Strekowski

Chin

and Salazar

Synthesis of Novel Near-infrared Cyanine Dyes for Metal Ion Determination. J. Heterocycl. Chem. 33, 1871–1876 (1996).

60.

W. P.

Anderson

C. J.

Kao

Nikiforovich

G. V.

Synthesis and Characterization of a Macrocyclic Near-infrared Optical Scaffold. J. Am. Chem. Soc. 125, 7766–7767 (2003).

61.

Pham

Weissleder

and Tung

C. H.

A Practical Approach for the Preparation of Monofunctional Azulenyl Squaraine. Tetrahedron Lett. 44, 3975–3978 (2003).

62.

Strekowski

Mason

C. J.

Lee

Gupta

Sowell

Synthesis of Water-soluble Near-infrared Cyanine Dyes Functionalized With (Succinimido)oxy Carbonyl Group. J. Heterocycl. Chem. 40, 913–916 (2003).

63.

Kawasaki

Oma

Sakaguchi

Tominaga

and Hirayama

Abnormal Binding of Indocyanine Green with Serum Proteins in a Patient with Dealyed ICG Clearance. Clin. Chim. Acta. 47, 39–43 (1973).

64.

Kamisaka

Listowsky

Betheil

J. J.

Arias

I. M.

Kawasaki

Competitive Binding of Bilirubin, Sulfobromophthalein, Indocyanine Green and Other Organic Anions to Human and Bovine Serum Albumin. Biochim. Biophys. Acta 365, 169–180 (1974).

65.

Landsman

Kwant

Mook

and Zijlstra

Light-absorbing Properties, Stability, and Spectral Stabilization of Indocyanine Green. J. Appl. Physiol. 40, 575–583 (1976).

66.

Ott

Keiding

Bass

Landsman

M. L.

Kwant

Intrinsic Hepatic Clearance of Indocyanine Green in the Pig: Dependence on Plasma Protein Concentration. Eur. J. Clin. Invest. 22, 347–357 (1992).

67.

Sutterer

Hardin

Benson

Krovetz

and Scheibler

Optical Behavior of Indocyanine Green Dye in Blood and in Aqeous Solution. Am. Heart. J. 72, 345–350 (1966).

68.

Rajagopalan

Uetrecht

Bugaj

J. E.

Achilefu

S. A.

and Dorshow

R. B.

Stabilization of the Optical Tracer Agent Indocyanine Green Using Noncovalent Interactions. Photochem. Photobiol. 71, 347–350 (2000).

69.

Folli

Wagnieres

Pelegrin

Calmes

J. M.

Braichotte

Immunophotodiagnosis of Colon Carcinomas in Patients Injected with Fluoresceinated Chimeric Antibodies Against Carcinoembryonic Antigen. Proc. Natl. Acad. Sci. USA 89, 7973–7977 (1992).

70.

Polzer

R. J.

Coffing

S. L.

Marcus

C. B.

Park

S. S.

Gelboin

H. V.

Inhibition of Benzo a Pyrene Metabolism by Insulin, Fitc-Insulin and an Fitc-Insulin-Antibody Conjugate in the Human Hepatoma-Cell Line Hepg2. Chem.-Biol. Interact. 97, 307–318 (1995).

71.

Wagnieres

G. A.

Studzinski

A. P.

and vandenBergh

H. E.

Endoscopic Fluorescence Imaging System for Simultaneous Visual Examination and Photodetection of Cancers. Rev. Sci. Instrum. 68, 203–212 (1997).

72.

Lazarev

V. V.

Roth

R. A.

Kazakevich

and Hang

Detection of Premalignant Oral Lesions in Hamsters with an Endoscopic Fluorescence Imaging System. Cancer 85, 1421–1429 (1999).

73.

Gannot

Garashi

Gannot

Chernomordik

and Gandjbakhche

In Vivo Quantitative Three-dimensional Localization of Tumor Labeled with Exogenous Specific Fluorescence Markers. Appl. Optics 42, 3073–3080 (2003).

74.

Achilefu

Jimenez

H. N.

Dorshow

R. B.

Bugaj

J. E.

Webb

E. G.

Synthesis, In Vitro Receptor Binding, and In Vivo Evaluation of Fluorescein and Carbocyanine Peptide-based Optical Contrast Agents. J. Med. Chem. 45, 2003–2015 (2002).

75.

Bellnier

D. A.

Greco

W. R.

Loewen

G. M.

Nava

Oseroff

A. R.

Population Pharmacokinetics of the Photodynamic Therapy Agent 2- 1-hexyloxyethyl-2-devinyl Pyropheophorbide-a in Cancer Patients. Cancer Res. 63, 1806–1813 (2003).

76.

Baas

vanGeel

I. P. J.

Oppelaar

Meyer

Beynen

J. H.

Enhancement of Photodynamic Therapy by Mitomycin C: A Preclinical and Clinical Study. Br. J. Cancer 73, 945–951 (1996).

77.

Kato

Furukawa

Sato

Okunaka

Kusunoki

Phase II Clinical Study of Photodynamic Therapy Using Mono-Laspartyl Chlorin e6 and Diode Laser for Early Superficial Squamous Cell Carcinoma of the Lung. Lung Cancer 42, 103–111 (2003).

78.

Schaffer

Ertl-Wagner

Schaffer

P. M.

Kulka

Hofstetter

Porphyrins as Radiosensitizing Agents for Solid Neoplasms. Curr. Pharm. Design 9, 2024–2035 (2003).

79.

Moghissi

and Dixon

Photodynamic Therapy (PDT) in Esophageal Cancer: A Surgical View of its Indications Based on 14 Years Experience. Technol. Cancer Res. Treat. 2, 319–326 (2003).

80.

Kostron

Obwegeser

and Jakober

Photodynamic Therapy in Neurosurgery: A Review. J. Photochem. Photobiol. B-Biol. 36, 157–168 (1996).

81.

Connelly

J. P.

Botchway

S. W.

Kunz

Pattison

Parker

A. W.

Time-resolved Fluorescence Imaging of Photosensitiser Distributions in Mammalian Cells Using a Picosecond Laser Line-scanning Microscope. J. Photochem. Photobiol. A-Chem. 142, 169–175 (2001).

82.

Fischer

Dickson

E. F.

Pottier

R. H.

and Wieland

An Affordable, Portable Fluorescence Imaging Device for Skin Lesion Detection Using a Dual Wavelength Approach for Image Contrast Enhancement and Aminolaevulinic Acid-induced Protoporphyrin IX. Part I. Design, Spectral and Spatial Characteristics. Lasers Med. Sci. 16, 199–206 (2001).

83.

Licha

in Contrast Agents Ii, Vol. 222, pp. 1–29. Springer-Verlag Berlin, Berlin (2002).

84.

Zhang

Z. H.

Blessington

Busch

T. M.

Pyropheophorbide 2-deoxyglucosamide: A New Photosensitizer Targeting Glucose Transporters. Bioconjugate Chem. 14, 709–714 (2003).

85.

Achilefu

Bugaj

J. E.

Dorshow

R. B.

and Rajagopalan

Tumor Targeted Photodiagnostic-phototherapeutic Agents. US Patent Application Publication 20030105300 A1. Published June 5 (2003).

86.

Achilefu

Rajagopalan

Dorshow

R. B.

and Bugaj

J. E.

Dyebioconjugates for Simultaneous Optical Diagnostic and Therapeutic Applications. US Patent Application Publication 20030152577 A1. Published August 14 (2003).

87.

Doyle

T. C.

Burns

S. M.

and Contag

C. H.

In Vivo Bioluminescence Imaging for Integrated Studies of Infection. Cell Microbiol. 6, 303–317 (2004).

88.

Contag

C. H.

Jenkins

Contag

F. R.

and Negrin

R. S.

Use of Reporter Genes for Optical Measurements of Neoplastic Disease In Vivo. Neoplasia 2, 41–52 (2000).

89.

Tsien

R. Y.

The Green Fluorescent Protein. Annu. Rev. Biochem. 67, 509–544 (1998).

90.

Yang

Baranov

Jiang

Sun

F. X.

X. M.

Whole-body Optical Imaging of Green Fluorescent Protein-expressing Tumors and Metastases. Proc. Natl. Acad. Sci. USA 97, 1206–1211 (2000).

91.

Ray

Pimenta

Paulmurugan

Berger

Phelps

M. E.

Noninvasive Quantitative Imaging of Protein-protein Interactions in Living Subjects. Proc. Natl. Acad. Sci. USA 99, 3105–3110 (2002).

92.

Bhaumik

and Gambhir

S. S.

Optical Imaging of Renilla Luciferase Reporter Gene Expression in Living Mice. Proc. Natl. Acad. Sci. USA 99, 377–382 (2002).

93.

Coralli

Cemazar

Kanthou

Tozer

G. M.

and Dachs

G. U.

Limitations of the Reporter Green Fluorescent Protein Under Simulated Tumor Conditions. Cancer Res. 61, 4784–4790 (2001).

94.

Zaveer

M. S.

and Zimmer

Structural Analysis of the Immature Form of the GFP Homologue DsRed. Bioorg. Med. Chem. Lett. 13, 3919–3922 (2003).

95.

Verkhusha

V. V.

Kuznetsova

I. M.

Stepanenko

O. V.

Zaraisky

A. G.

Shavlovsky

M. M.

High Stability of Discosoma DsRed as Compared to Aequorea EGFP. Biochemistry 42, 7879–7884 (2003).

96.

Fradkov

A. F.

Verkhusha

V. V.

Staroverov

D. B.

Bulina

M. E.

Yanushevich

Y. G.

Far-red Fluorescent Tag for Protein Labelling. Biochem. J. 368, 17–21 (2002).

97.

Verkhusha

V. V.

Otsuna

Awasaki

Oda

Tsukita

An Enhanced Mutant of Red Fluorescent Protein DsRed for Double Labeling and Developmental Timer of Neural Fiber Bundle Formation. J. Biol. Chem. 276, 29621–29624 (2001).

98.

Jakobs

Subramaniam

Schonle

Jovin

T. M.

and Hell

S. W.

EGFP and DsRed Expressing Cultures of Escherichia coli Imaged by Confocal, Two-photon and Fluorescence Lifetime Microscopy. FEBS Lett. 479, 131–135 (2000).

99.

Wang

Z. F.

Shah

J. V.

Chen

Z. P.

Sun

C. H.

and Berns

M. W.

Fluorescence Correlation Spectroscopy Investigation of a GFP Mutant-enhanced Cyan Fluorescent Protein and its Tubulin Fusion in Living Cells With Two-photon Excitation. J. Biomed. Opt. 9, 395–403 (2004).

100.

Kohl

Heinze

K. G.

Kuhlemann

Koltermann

and Schwille

A Protease Assay for Two-photon Crosscorrelation and FRET Analysis Based Solely on Fluorescent Proteins. Proc. Natl. Acad. Sci. USA 99, 12161–12166 (2002).

101.

Choy

O'Connor

Diehn

F. E.

Costouros

Alexander

H. R.

Comparison of Noninvasive Fluorescent and Bioluminescent Small Animal Optical Imaging. Biotechniques 35, 1022–1026, 1028–1030 (2003).

102.

Troy

Jekic-McMullen

Sambucetti

and Rice

Quantitative Comparison of the Sensitivity of Detection of Fluorescent and Bioluminescent Reporters in Animal Models. Molecular Imaging 3, 9–23 (2004).

103.

Massoud

T. F.

and Gambhir

S. S.

Molecular Imaging in Living Subjects: Seeing Fundamental Biological Processes in a New Light. Genes Dev. 17, 545–580 (2003).

104.

Goldman

E. R.

Balighian

E. D.

Mattoussi

Kuno

M. K.

Mauro

J. M.

Avidin: A Natural Bridge for Quantum Dot-antibody Conjugates. J. Am. Chem. Soc. 124, 6378–6382 (2002).

105.

Parak

W. J.

Gerion

Pellegrino

Zanchet

Micheel

Biological applications of colloidal nanocrystals. Nanotechnology 14, R15–R27 (2003).

106.

Geddes

C. D.

Cao

Gryczynski

Fang

J. Y.

Metal-enhanced Fluorescence (MEF) Due to Silver Colloids on a Planar Surface: Potential Applications of Indocyanine Green to In Vivo Imaging. J. Phys. Chem. A 107, 3443–3449 (2003).

107.

Josephson

Kircher

M. F.

Mahmood

Tang

and Weissleder

Near-infrared Fluorescent Nanoparticles as Combined MR/Optical Imaging Probes. Bioconjugate Chem. 13, 554–560 (2002).

108.

Manning

H. C.

Goebel

Marx

J. N.

and Bornhop

D. J.

Facile, Efficient Conjugation of a Trifunctional Lanthanide Chelate to a Pripheral Benzodiazepine Receptor Ligand. Org. Lett. 4, 1075–1078 (2002).

109.

Hubbard

D. S.

Houlne

M. P.

Kiefer

Janssen

H. F.

Hacker

Diagnostic Imaging Using Rare-earth Chelates. Lasers Med. Sci. 13, 14–21 (1998).

110.

Hubbard

D. S.

Houlne

M. P.

Kiefer

G. E.

McMillan

and Bornhop

D. J.

Endoscopic Fluorescence Imaging of Tissue Selective Lanthanide Chelates. Bioimaging 6, 63–70 (1998).

111.

Kang

J. S.

and Lakowicz

J. R.

Fluorescence Resonance Energy Transfer in Calf Thymus DNA From a Long-lifetime Metal-ligand Complex to Nile Blue. J. Biochem. Mol. Biol. 34, 551–558 (2001).

112.

Maliwal

B. P.

Gryczynski

and Lakowicz

J. R.

Long-wavelength Long-lifetime Luminophores. Anal. Chem. 73, 4277–4285 (2001).

113.

Barton

J. K.

Hoying

J. B.

and Sullivan

C. J.

Use of Microbubbles as an Optical Coherence Tomography Contrast Agent. Acad. Radiol. 9, S52–S55 (2002).

114.

Lee

T. M.

Oldenburg

A. L.

Sitafalwalla

Marks

D. L.

Luo

Engineered Microsphere Contrast Agents for Optical Coherence Tomography. Opt. Lett. 28, 1546–1548 (2003).

115.

Nioka

Yung

Shnall

Zhao

Orel

in Oxygen Transport to Tissue Xviii, Vol. 411, pp. 227–232. Plenum Pres Div Plenum Publishing Corp, New York (1997).

116.

Reynolds

J. S.

Troy

T. L.

Mayer

R. H.

Thompson

A. B.

Waters

D. J.

Imaging of Spontaneous Canine Mammary Tumors Using Fluorescent Contrast Agents. Photochem. Photobiol. 70, 87–94 (1999).

117.

Bremer

Tung

C. H.

Bogdanov

and Weissleder

Imaging of Differential Protease Expression in Breast Cancers for Detection of Aggressive Tumor Phenotypes. Radiology 222, 814–818 (2002).

118.

Bremer

Tung

C. H.

and Weissleder

In Vivo Molecular Target Assessment of Matrix Metalloproteinase Inhibition. Nat. Med. 7, 743–748 (2001).

119.

Weissleder

A Clearer Vision for In Vivo Imaging. Nat. Biotechnol. 19, 316–317 (2001).

120.

Weissleder

Tung

C. H.

Mahmood

and Bogdanov

In Vivo Imaging of Tumors with Protease-activated Near-infrared Fluorescent Probes. Nat. Biotechnol. 17, 375–378 (1999).

121.

Kohl-Bareis

Obrig

Steinbrink

Malak

Uludag

Noninvasive Monitoring of Cerebral Blood Flow by a Dye Bolus Method: Separation of Brain from Skin And Skull Signals. J. Biomed. Opt. 7, 464–470 (2002).

122.

Boehm

Hochmuth

Malich

Reichenbach

J. R.

Fleck

Contrast-enhanced Near-infrared Laser Mammography with a Prototype Breast Scanner — Feasibility Study with Tissue Phantoms and Preliminary Results of Imaging Experimental Tumors. Invest. Radiol. 36, 573–581 (2001).

123.

Y. Q.

Qian

Z. Y.

Chen

J. X.

Blessington

Ramanujam

High-resolution Three-dimensional Scanning Optical Image System for Intrinsic and Extrinsic Contrast Agents in Tissue. Rev. Sci. Instrum. 73, 172–178 (2002).

124.

Licha

Riefke

Ntziachristos

Becker

Chance

Hydrophilic Cyanine Dyes as Contrast Agents for Near-infrared Tumor Imaging: Synthesis, Photophysical Properties and Spectroscopic In Vivo Characterization. Photochem. Photobiol. 72, 392–398 (2000).

125.

Ntziachristos

Bremer

and Weissleder

Fluorescence Imaging with Near-infrared Light: New Technological Advances that Enable In Vivo Molecular Imaging. Eur. Radiol. 13, 195–208 (2003).

126.

Rudin

and Weissleder

Molecular Imaging in Drug Discovery and Development. Nat. Rev. Drug Discov. 2, 123–131 (2003).

127.

Mariani

Lasku

Balza

Gaggero

Motta

Tumor Targeting Potential of the Monoclonal Antibody BC-1 Against Oncofetal Fibronectin in Nude Mice Bearing Human Tumor Implants. Cancer 80, 2378–2384 (1997).

128.

Ballou

Fisher

G. W.

Hakala

T. R.

and Farkas

D. L.

Tumor Detection and Visualization Using Cyanine Fluorochrome-labeled Antibodies. Biotechnol. Prog. 13, 649–658 (1997).

129.

Ballou

Fisher

G. W.

Deng

J. S.

Hakala

T. R.

Srivastava

Cyanine Fluorochrome-labeled Antibodies In Vivo: Assessment of Tumor Imaging Using Cy3, Cy5, Cy5.5, and Cy7. Cancer Detect. Prev. 22, 251–257 (1998).

130.

Pelegrin

Xavier

Barbet

Bartholeyns

Baty

Immuno-targeting of Tumors: State of the Art and Prospects in 2000. Bull. Cancer 87, 777–791 (2000).

131.

Muguruma

Ito

Bando

Taoka

Kusaka

Labeled Carcinoembryonic Antigen Antibodies Excitable by Infrared Rays: A Novel Diagnostic Method for Micro Cancers in the Digestive Tract. Intern. Med. 38, 537–542 (1999).

132.

Soukos

N. S.

Hamblin

M. R.

Keel

Fabian

R. L.

Deutsch

T. F.

Epidermal Growth Factor Receptor-targeted Immunophotodiagnosis and Photoimmunotherapy of Oral Precancer In Vivo. Cancer Res. 61, 4490–4496 (2001).

133.

Becker

Riefke

Ebert

Sukowski

Rinneberg

Macromolecular Contrast Agents for Optical Imaging of Tumors: Comparison of Indotricarbocyanine-labeled Human Serum Albumin and Transferrin. Photochem. Photobiol. 72, 234–241 (2000).

134.

Ramjiawan

Maiti

Aftanas

Kaplan

Fast

Noninvasive Localization of Tumors by Immunofluorescence Imaging Using a Single Chain Fv Fragment of a Human Monoclonal Antibody with Broad Cancer Specificity. Cancer 89, 1134–1144 (2000).

135.

Ito

Muguruma

Kusaka

Tadatsu

Inayama

Detection of Human Gastric Cancer in Resected Specimens using a Novel Infrared Fluorescent Anti-human Carcinoembryonic Antigen Antibody with an Infrared Fluorescence Endoscope In Vitro. Endoscopy 33, 849–853 (2001).

136.

Valesky

Spang

A. J.

Fisher

G. W.

Farkas

D. L.

and Becker

Noninvasive Dynamic Fluorescence Imaging of Human Melanomas Reveals that Targeted Inhibition of bFGF or FGFR-1 in Melanoma Cells Blocks Tumor Growth by Apoptosis. Mol. Med. 8, 103–112 (2002).

137.

Bando

Muguruma

Ito

Musashi

Inayama

Basic Studies on a Labeled Anti-mucin Antibody Detectable by Infrared -fluorescence Endoscopy. J. Gastroenterol. 37, 260–269 (2002).

138.

Ilias

Bollas

Batsakis

and Christakopoulou

Tc-99m-labeled Monoclonal Antibody Fragment Imaging in a Patient with Fever of Unknown Origin. Clin. Nucl. Med. 28, 981–983 (2003).

139.

Mohamed

I. E.

Braun

D. P.

Fanning

Andrews

S. J.

Skeel

R. T.

A Phase I/II Pharmacokinetic and Dose Escalation Study of H11 scFv (A Human Monoclonal Antibody Fragment). Breast Cancer Res. Treat. 76, S115–S115 (2002).

140.

Ramjiawan

Maiti

Kaplan

Fast

Mantsch

H. H.

In Vivo Monitoring of the Distribution of a Monoclonal Antibody Fragment. Vib. Spectrosc. 28, 177–188 (2002).

141.

Palestro

C. J.

Love

Marwin

S. E.

Tomas

M. B.

and Bhargava

K. K.

Monoclonal Antibody Fragment Imaging of Osteomyelitis: Enhanced Specificity of Semiquantitative Analysis. J. Nucl. Med. 39, 33P–33P (1998).

142.

Juweid

Sharkey

R. M.

Behr

T. M.

Swayne

L. C.

Dunn

Clinical Evaluation of Tumor Targeting with the Anticarcinoembryonic Antigen Murine Monoclonal Antibody Fragment, MN-14 F(ab)(2). Cancer 78, 157–168 (1996).

143.

Morris

J. F.

Krishnamurthy

Antonovic

Duncan

Turner

F. E.

Tc-99m Monoclonal-Antibody Fragment (Fab) Scintigraphy in the Evaluation of Small-Cell Lung-Cancer — A Preliminary-Report. Nucl. Med. Biol. 18, 613-& (1991).

144.

Reubi

J. C.

Waser

Schaer

J. C.

and Laissue

J. A.

Somatostatin Receptor sst1-sst5 Expression in Normal and Neoplastic Human Tissues Using Receptor Autoradiography with Subtype-selective Ligands. Eur. J. Nucl. Med. 28, 836–846 (2001).

145.

Wangberg

Nilsson

Johanson

V. V.

Kolby

Forssell-Aronsson

Somatostatin Receptors in the Diagnosis and Therapy of Neuroendocrine Tumor. Oncologist 2, 50–58 (1997).

146.

Froidevaux

and Eberle

A. N.

Somatostatin Analogs and Radiopeptides in Cancer Therapy. Biopolymers 66, 161–183 (2002).

147.

de Herder

W. W.

and Lamberts

S. W. J.

Somatostatin and Somatostatin Analogues: Diagnostic and Therapeutic Uses. Curr. Opin. Oncol. 14, 53–57 (2002).

148.

Balon

H. R.

Goldsmith

S. J.

Siegel

B. A.

Silberstein

E. B.

Krenning

E. P.

Procedure Guideline for Somatostatin Receptor Scintigraphy with In-111-pentetreotide. J. Nucl. Med. 42, 1134–1138 (2001).

149.

Lebtahi

Le Cloirec

Houzard

Daou

Sobhani

Detection of Neuroendocrine Tumors: Tc-99m-P829 Scintigraphy Compared with In-111-pentetreotide Scintigraphy. J. Nucl. Med. 43, 889–895 (2002).

150.

Webb

S. M.

and Mones

Twenty-two Years' Survival of Metastatic Gastrinoma Evidenced Recently by Somatostatin-receptor-specific Scintigraphy. Eur. J. Gastroenterol. Hepatol. 14, 333–336 (2002).

151.

Kwekkeboom

D. J.

Bakker

W. H.

Kooij

P. P. M.

Konijnenberg

M. W.

Srinivasan

Lu-177-DOTA(0),Tyr(3) Octreotate: Comparison with In-111- DTPA(0) Octreotide in Patients. Eur. J. Nucl. Med. 28, 1319–1325 (2001).

152.

Licha

Hessenius

Becker

Henklein

Bauer

Synthesis, Characterization, and Biological Properties of Cyanine-labeled Somatostatin Analogues as Receptor-targeted Fluorescent Probes. Bioconjugate Chem. 12, 44–50 (2001).

153.

Becker

Hessenius

Licha

Ebert

Sukowski

Receptor-targeted Optical Imaging of Tumors with Near-infrared Fluorescent Ligands. Nat. Biotechnol. 19, 327–331 (2001).

154.

Bugaj

J. E.

Achilefu

Dorshow

R. B.

and Rajagopalan

Novel Fluorescent Contrast Agents for Optical Imaging of In Vivo Tumors Based on a Receptor-targeted Dye-peptide Conjugate Platform. J. Biomed. Opt. 6, 122–133 (2001).

155.

Zhou

J. H.

Chen

Mokotoff

Zhong

R. K.

Shultz

L. D.

Bombesin/Gastrin-releasing Peptide Receptor: A Potential Target for Antibody-mediated Therapy of Small Cell Lung Cancer. Clin. Cancer Res. 9, 4953–4960 (2003).

156.

Nock

Nikolopoulou

Chiotellis

Loudos

Maintas

Tc-99m Demobesin 1, A Novel Potent Bombesin Analogue for GRP Receptor-targeted Tumour Imaging. Eur. J. Nucl. Med. Mol. Imaging 30, 247–258 (2003).

157.

Zinn

K. R.

and Chaudhuri

T. R.

The Type 2 Human Somatostatin Receptor as a Platform for Reporter Gene Imaging. Eur. J. Nucl. Med. Mol. Imaging 29, 388–399 (2002).

158.

Scopinaro

De Vincentis

Varvarigou

A. D.

Laurenti

Iori

Tc-99m-bombesin Detects Prostate Cancer and Invasion of Pelvic Lymph Nodes. Eur. J. Nucl. Med. Mol. Imaging 30, 1378–1382 (2003).

159.

Okarvi

S. M.

and Al-Jammaz

Synthesis, Radiolabelling and Biological Characteristics of a Bombesin Peptide Analog as a Tumor Imaging Agent. Anticancer Res. 23, 2745–2750 (2003).

160.

Yegen

B. C.

Bombesin-like Peptides: Candidates as Diagnostic and Therapeutic Tools. Curr. Pharm. Design 9, 1013–1022 (2003).

161.

Hoffman

T. J.

Gali

Smith

C. J.

Sieckman

G. L.

Hayes

D. L.

Novel Series of In-111-labeled Bombesin Analogs as Potential Radiopharmaceuticals for Specific Targeting of Gastrin-releasing Peptide Receptors Expressed on Human Prostate Cancer Cells. J. Nucl. Med. 44, 823–831 (2003).

162.

Kiaris

Schally

A. V.

Nagy

Sun

Armatis

Targeted Cytotoxic Analogue of Bombesin/Gastrin Releasing Peptide Inhibits the Growth of H-69 Human Small-cell Lung Carcinoma in Nude Mice. Br. J. Cancer 81, 966–971 (1999).

163.

Chave

H. S.

Gough

A. C.

Palmer

Preston

S. R.

and Primrose

J. N.

Bombesin Family Receptor and Ligand Gene Expression in Human Colorectal Cancer and Normal Mucosa. Br. J. Cancer 82, 124–130 (2000).

164.

Behr

T. M.

Gotthardt

Barth

and Behe

Imaging Tumors with Peptide-based Radioligands. Q. J. Nucl. Med. 45, 189–200 (2001).

165.

Hoffman

T. J.

Quinn

T. P.

and Volkert

W. A.

Radiometallated Receptor-avid Peptide Conjugates for Specific In Vivo Targeting of Cancer Cells. Nucl. Med. Biol. 28, 527–539 (2001).

166.

Sun

B. D.

Halmos

Schally

A. V.

Wang

X. F.

and Martinez

Presence of Receptors for Bombesin/Gastrin-releasing Peptide and mRNA for Three Receptor Subtypes in Human Prostate Cancers. Prostate 42, 295–303 (2000).

167.

Bajo

A. M.

Schally

A. V.

Groot

and Szepeshazi

Bombesin Antagonists Inhibit Proangiogenic Factors in Human Experimental Breast Cancers. Br. J. Cancer 90, 245–252 (2004).

168.

Bajo

A. M.

Schally

A. V.

Krupa

Hebert

Groot

Bombesin Antagonists Inhibit Growth of MDA-MB-435 Estrogen-independent Breast Cancers and Decrease the Expression of the ErbB-2/HER-2 Oncoprotein and c-jun and c-fos Oncogenes. Proc. Natl. Acad. Sci. USA 99, 3836–3841 (2002).

169.

Reubi

J. C.

Wenger

Schmuckli-Maurer

Schaer

J. C.

and Gugger

Bombesin Receptor Subtypes in Human Cancers: Detection with the Universal Radioligand I-125-D-TYR6, Beta-ALA(11), PHE13, NLE14 Bombesin(6–14). Clin. Cancer Res. 8, 1139–1146 (2002).

170.

Karra

S. R.

Schibli

Gali

Katti

K. V.

Hoffman

T. J.

Tc-99m-labeling and In Vivo Studies of a Bombesin Analogue with a Novel Water-soluble dithiadiphosphine-based Bifunctional Chelating Agent. Bioconjugate Chem. 10, 254–260 (1999).

171.

Van de Wiele

Dumont

Vanden Broecke

Oosterlinck

Cocquyt

Technetium-99m RP527, a GRP Analogue for Visualisation of GRP Receptor-expressing Malignancies: A Feasibility Study. Eur. J. Nucl. Med. 27, 1694–1699 (2000).

172.

Markwalder

and Reubi

J. C.

Gastrin-releasing Peptide Receptors in the Human Prostate: Relation to Neoplastic Transformation. Cancer Res. 59, 1152–1159 (1999).

173.

Friry

Feliciangeli

Richard

Kitabgi

and Rovere

Production of Recombinant Large Proneurotensin Neuromedin N-derived Peptides and Characterization of their Binding and Biological Activity. Biochem. Biophys. Res. Commun. 290, 1161–1168 (2002).

174.

Guha

Rey

and Rozengurt

Neurotensin Induces Protein Kinase C-dependent Protein Kinase D Activation and DNA Synthesis in Human Pancreatic Carcinoma Cell Line PANC-1. Gastroenterology 122, A136–A136 (2002).

175.

Wang

Friess

Zhu

Z. W.

Graber

Zimmermann

Neurotensin Receptor-1 mRNA Analysis in Normal Pancreas and Pancreatic Disease. Clin. Cancer Res. 6, 566–571 (2000).

176.

Ehlers

R. A.

Kim

S. H.

Zhang

Y. J.

Ethridge

R. T.

Murrilo

Gut Peptide Receptor Expression in Human Pancreatic Cancers. Ann. Surg. 231, 838–846 (2000).

177.

Chavatte

Terriere

Jeannin

Iterbeke

Briejer

Labelling and Evaluation of New Stabilised Neurotensin (8–13) Analogues for Single Photon Emission Tomography (SPET). J. Label. Compd. Radiopharm. 42, 423–435 (1999).

178.

Breeman

W. A. P.

de Jong

Erion

J. L.

Bugaj

J. E.

Srinivasan

Preclinical Comparison of In-111-labeled DTPA- or DOTA-bombesin Analogs for Receptor-targeted Scintigraphy and Radionuclide Therapy. J. Nucl. Med. 43, 1650–1656 (2002).

179.

Garcia-Garayoa

Blauenstein

Bruehlmeier

Blanc

Iterbeke

Preclinical Evaluation of a New, Stabilized Neurotensin(8–13) Pseudopeptide Radiolabeled with Tc-99m. J. Nucl. Med. 43, 374–383 (2002).

180.

Garcia-Garayoa

Allemann-Tannahill

Blauenstein

Willmann

Carrel-Remy

In Vitro and In Vivo Evaluation of New Radiolabeled Neurotensin(8–13) Analogues with High Affinity for NT1 Receptors. Nucl. Med. Biol. 28, 75–84 (2001).

181.

Feng

H. J.

Zaidi

Cusack

and Richelson

Synthesis and Biological Studies of Novel Neurotensin(8–13) Mimetics. Bioorg. Med. Chem. 10, 3849–3858 (2002).

182.

Leyton

Garcia-Marin

Jensen

R. T.

and Moody

T. W.

Neurotensin Causes Tyrosine Phosphorylation of Focal Adhesion Kinase in Lung Cancer Cells. Eur. J. Pharmacol. 442, 179–186 (2002).

183.

Lundquist

J. T.

and Dix

T. A.

Preparation and Receptor Binding Affinities of Cyclic C-terminal Neurotensin (8–13) and (9–13) Analogues. Bioorg. Med. Chem. Lett. 9, 2579–2582 (1999).

184.

Lugrin

Vecchini

Doulut

Rodriguez

Martinez

Reduced Peptide-Bond Pseudopeptide Analogs of Neurotensin — Binding and Biological-Activities, and In Vitro Metabolic Stability. Eur. J. Pharmacol. 205, 191–198 (1991).

185.

Gonzalezmuniz

Garcialopez

M. T.

Gomezmonterrey

Herranz

Jimeno

M. L.

Ketomethylene and (Cyanomethylene) Amino Pseudopeptide Analogs of the C-Terminal Hexapeptide of Neurotensin. J. Med. Chem. 38, 1015–1021 (1995).

186.

Achilefu

Srinivasan

Schmidt

M. A.

Jimenez

H. N.

Bugaj

J. E.

Novel Bioactive and Stable Neurotensin Peptide Analogues Capable of Delivering Radiopharmaceuticals and Molecular Beacons to Tumors. J. Med. Chem. 46, 3403–3411 (2003).

187.

Reddy

J. A.

and Low

P. S.

Folate-mediated Targeting of Therapeutic and Imaging Agents to Cancers. Crit. Rev. Ther. Drug Carr. Syst. 15, 587–627 (1998).

188.

Leamon

C. P.

and Low

P. S.

Folate-mediated Targeting: From Diagnostics to Drug and Gene Delivery. Drug Discov. Today 6, 44–51 (2001).

189.

Sudimack

and Lee

R. J.

Targeted Drug Delivery via the Folate Receptor. Adv. Drug Deliv. Rev. 41, 147–162 (2000).

190.

Leamon

C. P.

and Low

P. S.

Delivery of Macromolecules Into Living Cells — A Method That Exploits Folate Receptor Endocytosis. Proc. Natl. Acad. Sci. USA 88, 5572–5576 (1991).

191.

Wiener

E. C.

Konda

Shadron

Brechbiel

and Gansow

Targeting Dendrimer-chelates to Tumors and Tumor Cells Expressing the High-affinity Folate Receptor. Invest. Radiol. 32, 748–754 (1997).

192.

Chen

Wong

K. F.

Fenske

D. B.

Palmer

L. R.

and Cullis

P. R.

Fluorescent-labeled Poly(ethylene glycol) Lipid Conjugates with Distal Cationic Headgroups. Bioconjugate Chem. 11, 433–437 (2000).

193.

Kennedy

M. D.

Jallad

K. N.

Thompson

D. H.

Ben-Amotz

and Low

P. S.

Optical Imaging of Metastatic Tumors Using a Folate-targeted Fluorescent Probe. J. Biomed. Opt. 8, 636–641 (2003).

194.

Moon

W. K.

Lin

Y. H.

O'Loughlin

Tang

Kim

D. E.

Enhanced Tumor Detection Using a Folate Receptor-targeted Near-infrared Fluorochrome Conjugate. Bioconjugate Chem. 14, 539–545 (2003).

195.

Tung

C. H.

Lin

Y. H.

Moon

W. K.

and Weissleder

R. A.

Receptor-targeted Near-infrared Fluorescence Probe for In Vivo Tumor Imaging. Chembiochem 3, 784–786 (2002).

196.

Nice

E. C.

Domagala

Fabri

Nerriea

Walker

Rapid Microscale Enzymic Semisynthesis of Epidermal Growth Factor (EGF) Analogues. Growth Factors 20, 71–80 (2002).

197.

Wen

X. X.

Gurfinkel

Charnsangavej

Wallace

Near-infrared Optical Imaging of Epidermal Growth Factor Receptor in Breast Cancer Xenografts. Cancer Res. 63, 7870–7875 (2003).

198.

Whitson

K. B.

Beechem

J. M.

Beth

A. H.

and Staros

J. V.

Preparation and Characterization of Alexa Fluor 594-labeled Epidermal Growth Factor for Fluorescence Resonance Energy Transfer Studies: Application to the Epidermal Growth Factor Receptor. Anal Biochem 324, 227–236 (2004).

199.

Sokolov

Follen

Aaron

Pavlova

Malpica

Real-time Vital Optical Imaging of Precancer Using Anti-epidermal Growth Factor Receptor Antibodies Conjugated to Gold Nanoparticles. Cancer Res 63, 1999–2004 (2003).

200.

Bhargava

Licha

Knaute

Ebert

Becker

A Complete Substitutional Analysis of VIP for Better Tumor Imaging Properties. J. Mol. Recognit. 15, 145–153 (2002).

201.

Zaheer

Lenkinski

R. E.

Mahmood

Jones

A. G.

Cantley

L. C.

In Vivo Near-infrared Fluorescence Imaging of Osteoblastic Activity. Nat. Biotechnol. 19, 1148–1154 (2001).

202.

Lenkinski

R. E.

Ahmed

Zaheer

Frangioni

J. V.

and Goldberg

S. N.

Near-infrared Fluorescence Imaging of Microcalcification in an Animal Model of Breast Cancer. Acad. Radiol. 10, 1159–1164 (2003).

203.

Chen

Zheng

Zhang

Z. H.

Blessington

Zhang

Metabolism-enhanced Tumor Localization by Fluorescence Imaging: In Vivo Animal Studies. Opt. Lett. 28, 2070–2072 (2003).

204.

Pauwels

E. K. J.

Ribeiro

M. J.

Stoot

McCready

V. R.

Bourguignon

FDG Accumulation and Tumor Biology. Nucl. Med. Biol. 25, 317–322 (1998).

205.

Gambhir

S. S.

Molecular Imaging of Cancer with Positron Emission Tomography. Nat. Rev. Cancer 2, 683–693 (2002).

206.

Yamada

Nakata

Horimoto

Saito

Matsuoka

Measurement of Glucose Uptake and Intracellular Calcium Concentration in Single, Living Pancreatic Beta-cells. J. Biol. Chem. 275, 22278–22283 (2000).

207.

Bloch

and Achilefu

Polyvalent Carbocyanine Molecular Beacons for Molecular Recognitions. J. Am. Chem. Soc. 126, 7740–7741 (2004).